Value of the CHA2DS2-VASc score and Fabry-specific score for predicting new-onset or recurrent stroke/TIA in Fabry disease patients without atrial fibrillation

Dan Liu, Kai Hu, Marie Schmidt, Jonas Müntze, Octavian Maniuc, Daniel Gensler, Daniel Oder, Tim Salinger, Frank Weidemann, Georg Ertl, Stefan Frantz, Christoph Wanner, Peter Nordbeck, Dan Liu, Kai Hu, Marie Schmidt, Jonas Müntze, Octavian Maniuc, Daniel Gensler, Daniel Oder, Tim Salinger, Frank Weidemann, Georg Ertl, Stefan Frantz, Christoph Wanner, Peter Nordbeck

Abstract

Objectives: To evaluate potential risk factors for stroke or transient ischemic attacks (TIA) and to test the feasibility and efficacy of a Fabry-specific stroke risk score in Fabry disease (FD) patients without atrial fibrillation (AF).

Background: FD patients often experience cerebrovascular events (stroke/TIA) at young age.

Methods: 159 genetically confirmed FD patients without AF (aged 40 ± 14 years, 42.1% male) were included, and risk factors for stroke/TIA events were determined. All patients were followed up over a median period of 60 (quartiles 35-90) months. The pre-defined primary outcomes included new-onset or recurrent stroke/TIA and all-cause death.

Results: Prior stroke/TIA (HR 19.97, P < .001), angiokeratoma (HR 4.06, P = .010), elevated creatinine (HR 3.74, P = .011), significant left ventricular hypertrophy (HR 4.07, P = .017), and reduced global systolic strain (GLS, HR 5.19, P = .002) remained as independent risk predictors of new-onset or recurrent stroke/TIA in FD patients without AF. A Fabry-specific score was established based on above defined risk factors, proving somehow superior to the CHA2DS2-VASc score in predicting new-onset or recurrent stroke/TIA in this cohort (AUC 0.87 vs. 0.75, P = .199).

Conclusions: Prior stroke/TIA, angiokeratoma, renal dysfunction, left ventricular hypertrophy, and global systolic dysfunction are independent risk factors for new-onset or recurrent stroke/TIA in FD patients without AF. It is feasible to predict new or recurrent cerebral events with the Fabry-specific score based on the above defined risk factors. Future studies are warranted to test if FD patients with high risk for new-onset or recurrent stroke/TIA, as defined by the Fabry-specific score (≥ 2 points), might benefit from antithrombotic therapy. Clinical trial registration HEAL-FABRY (evaluation of HEArt invoLvement in patients with FABRY disease, NCT03362164).

Keywords: Fabry disease; Global systolic strain; Stroke; Transient ischemic attack.

Conflict of interest statement

P. Nordbeck, C. Wanner and F. Weidemann received speaker and/or advisory board honoraria from Amicus, Genzyme and Shire corporations. Research grants were given to the Institution by Genzyme and Shire corporations.

Figures

Fig. 1
Fig. 1
Diagnostic performance of the CHA2DS2-VASc score and the Fabry-specific score for predicting new-onset or recurrent stroke/TIA (a) and all-cause mortality (b) in Fabry patients without atrial fibrillation
Fig. 2
Fig. 2
Cumulative hazard of new-onset or recurrent stroke/TIA in FD patients without atrial fibrillation stratified by low, intermediate, and high risk identified using the CHA2DS2-VASc score (a) and the Fabry-specific score (b)

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